PROJECT SUMMARY This proposal seeks continued support, via an institutional training grant, for a training program for pre and postdoctoral fellows who will pursue research careers that focus on genetic influences on substance abuse. The faculty, from the Institute for Behavioral Genetics (IBG) and collaborating units, is distinguished and active in research, and IBG scientists have actively pursued studies of genetic influences on substance abuse for over 50 years. Major substance abuse-related research projects are in progress in both human and animal behavior genetics. The application of biometrical, statistical, and quantitative genetic techniques, together with bioinformatics, genome-wide analyses and next generation sequencing, and epigenetics, is providing real advances in knowledge. Neuro-chemical, -pharmacological, -physiological, and molecular genetic studies, are providing an understanding of gene function related to behavior. Since our last application, we have added a major commitment to functional and structural brain imaging as a research tool and have expanded our faculty and training program accordingly. Our research and training include the use of large scale collaborative studies that are amassing DNA repositories and rich phenotypic data sets available for studies of substance abuse. These include the Adolescent Brain Cognitive Development (ABCD) study, for which our training faculty are PIs of the twin study component, the NIDA Genetics Consortium, the Psychiatric Genetics Consortium, the UK Biobank, and GSCAN, a genome wide study of over 1 million cases. IBG facilities are available for gene function and expression studies, and behavioral, biochemical, and neurophysiological studies, and we are actively pursuing animal model studies of the functional implications of SNPs robustly associated with drug phenotypes in the human population. To reflect the expanded need for training, particularly for genetics expertise applied in the context of ABCD, brain imaging, translational research, and `big data' studies, funds are requested to support 6 pre-doctoral and 3 postdoctoral trainees. Trainees will typically be supported for up to 3 years. Pre-doctoral trainees receive doctorate degrees from a cooperating academic unit and certification in behavior genetics. Academic requirements in the training program include training in behavior genetics, quantitative and biometrical genetics, theoretical and computer-based statistics, molecular genetics, neuroscience, bioinformatics and genomics, mandatory training in the responsible conduct of research, and courses on behavioral, brain imaging, and clinical phenotypes. Additional requirements vary according to the degree granting academic unit. Research is an integral part of training. Postdoctoral trainees also pursue a formalized program that emphasizes individual research as well as competence in molecular and quantitative behavior genetics. Other activities in preparation for research careers in substance abuse include: supervision of students and/or technicians, hosting of seminar speakers and conference organization, guest lecturing, a weekly journal club, grant writing, and the development of individual professional plans.